This is a proposal to examine the pathobiology of patients with tuberculoid and lepromatous leprosy. In particular, we will define the cellular mechanisms necessary to mount a cell mediated response to M. leprae and to uncover the defects which result in the extensive replication of M. leprae in cutaneous macrophages. For this purpose we will analyze cells obtained from peripheral blood and the dermal lesions by both morphologic and functional studies. Each step in the triggering of T cells, the production of lymphokines and the activation of mononuclear phagocytes to a microbicidal state will be examined. The possible suppressor qualities of T cells and monocytes and soluble factors derived from them will be studied with M. laprae, other purified antigens and lectins, T cell triggering will be monitored by their replication and secretion of IL-2 and Gamma-IFN. Possible defects at the local dermal lesion will be analyzed. The ability of patients to mount a delayed hypersensitivity reaction and mobilize the appropriate subsets of immune cells will be assessed. The capacity of dermal macrophages to ingest, incorporate into a phagolysosome and kill M. leprae in the presence or absence of exogenous Gamma-IFN will be examined.